Shin Joon-Shik, Park Namhee, Ra Jehyeon, Kim Yangseok, Shin Minkyu, Hong Moochang, Kim Sung-Hoon, Kwon Ha-Jeong, Hong Seon-Pyo, Kim Jinju, Bae Hyunsu
Jaseng Hospital of Oriental Medicine, Sinsa-dong, Kangnam-gu, Seoul 135-896, Republic of Korea.
J Ethnopharmacol. 2009 Jul 30;124(3):397-403. doi: 10.1016/j.jep.2009.05.036. Epub 2009 Jun 6.
The destruction of cartilage in patients with osteoarthritis occurs due to an imbalance between matrix synthesis and degradation. Cartilage degradation is induced by the activation of matrix metalloproteinases (MMPs). Therefore, this study was conducted to evaluate the cartilage protective effect of Panax ginseng C.A. Meyer (PG).
S12 cells were treated with various concentrations of extract of PG and gensenosides Rd and Rb(3) for 3h, after which 10 ng/ml interleukin-1beta (IL-1beta) was added to the culture media. The levels of MMP3 in the conditioned media were then evaluated using an enzyme-linked immunosorbent assay (ELISA). In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of Type II Collagen and Pro-collagenase. Furthermore, Western blot analysis was performed to identify the roles that PG played in the ERK and p38 signaling pathways.
The MMP3 secretion levels of S12 cells were significantly lowered in response to treatment with PG and gensenosides Rd and Rb(3) at a concentration of 100 microg/ml when compared to cells that were treated with IL-1beta. In addition, PG induced the mRNA expression of Type II Collagen dose dependently. Furthermore, phosphorylated p38 and ERK were detected in S12 articular cartilage cell line that was treated with IL-1beta. PG decreased the phosphorylation of p38, but PG did not exert any effect on phospho-ERK.
These findings indicate that PG and gensenosides Rd and Rb(3) suppress MMP3 secretion and that gensenosides Rd and Rb(3) are the major elements involved in the suppression of MMP3 by PG. Furthermore, the suppression of MMP3 by PG occurs via the inhibition of phospho-p38 activation. Therefore, PG may exert a protective effect against the cartilage degradation of OA.
骨关节炎患者软骨的破坏是由于基质合成与降解之间的失衡所致。软骨降解是由基质金属蛋白酶（MMPs）的激活所诱导。因此，本研究旨在评估人参（PG）对软骨的保护作用。
用不同浓度的PG提取物、人参皂苷Rd和Rb(3)处理S12细胞3小时，之后向培养基中加入10 ng/ml白细胞介素-1β（IL-1β）。然后使用酶联免疫吸附测定（ELISA）评估条件培养基中MMP3的水平。此外，采用逆转录聚合酶链反应（RT-PCR）评估II型胶原蛋白和前胶原酶的mRNA表达。此外，进行蛋白质印迹分析以确定PG在ERK和p38信号通路中所起的作用。
与用IL-1β处理的细胞相比，当用浓度为100μg/ml的PG、人参皂苷Rd和Rb(3)处理时，S12细胞的MMP3分泌水平显著降低。此外，PG剂量依赖性地诱导II型胶原蛋白的mRNA表达。此外，在用IL-1β处理的S12关节软骨细胞系中检测到磷酸化的p38和ERK。PG降低了p38的磷酸化，但PG对磷酸化的ERK没有任何影响。
这些发现表明，PG、人参皂苷Rd和Rb(3)可抑制MMP3分泌，且人参皂苷Rd和Rb(3)是PG抑制MMP3的主要成分。此外，PG通过抑制磷酸化p38的激活来抑制MMP3。因此，PG可能对骨关节炎的软骨降解发挥保护作用。
